不同途径茶多酚对兔急性呼吸窘迫综合征肺保护的研究

Protective effects of different administration routes of tea polyphenol on lung protection of rabbits with acute respiratory distress syndrome

目的:观察茶多酚通过不同途径给药对急性呼吸窘迫综合征(ARDS)动物模型的干预作用,初步探讨茶多酚对ARDS炎症反应的抑制效果及可能的作用机制。方法:静脉注射油酸制备兔ARDS模型,40只大耳白兔被随机分为对照组(A组)、茶多酚高剂量(100 m g/kg)灌胃组(B组)、茶多酚低剂量(50 m g/kg)灌胃组(C组)、茶多酚高剂量(100 m g/kg)雾化组(D组)、茶多酚低剂量(50 m g/kg)雾化组(E组),每组8只。对照组采用单纯机械通气+常规治疗;其余给药各组制模后按不同途径给予相应药物,其余处理同对照组,4 h后结束实验。每小时进行一次血气分析,实验结束后处死动物,取左肺下叶中部约1 cm×1 cm×1 cm组织块,用体积分数为10%的中性甲醛固定。免疫组化法测定核转录因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)的阳性表达。结果:雾化组机械通气4 h动脉血氧分压(PaO2)明显高于对照组和灌胃组,动脉血二氧化碳分压(PaCO2)明显低于对照组和灌胃组,差异均有显著性(P均<0.01),但雾化两组间比较差异无显著性;对照组和灌胃组肺组织病理学改变明显比雾化组严重,雾化两组之间改变基本相似;雾化组肺组织中NF-κB、TNF-α、IL-1的阳性高表达明显低于对照组和灌胃组,低表达明显高于对照组和灌胃组,差异均有显著性(P均<0.05),雾化两组之间表达相似;对照组和灌胃组比较,上述指标差异均无显著性。结论:茶多酚雾化吸入对ARDS肺有保护作用,可减少肺组织中NF-κB、TNF-α、IL-1的阳性表达,减轻ARDS肺病理改变,改善ARDS的临床表现;而茶多酚灌胃无上述作用。

Objective： To observe the difference in interfering effect of tea polyphenol on animal model with acute respiratory distress syndrome （ARDS） via different routes of administration and preliminarily approach the inhibitory effect of tea polyphenol on the inflammatory reaction of ARDS and its possible mechanism. Methods： The models of ARDS rabbits were reproduced by intravenous injection of oleic acid. Then forty rabbits were randomly divided into control group （group A）, stomach infusion groups （100 mg/kg tea polyphenol was given through gastric tube to group B and 50 mg/kg to group C） and atomization groups （100 mg/kg tea polyphenol was given through atomization to group D and 50 mg/kg to group E, each group n=8） with the same ventilator parameters among the different groups. Then the models were sacrificed after mechanical ventilation for 4 hours. Blood gas was recorded and analyzed every hour after ARDS. A piece of lung tissue 1 cm× 1 cm× 1 cm in size was taken from the middle part of the left lower lobe of the lung after the animal was sacrificed. The tissue was preserved in 10% formalin for fixation. Positive expressions of nuclear factor - κB （NF - κB）, tumor necrosis factor - α （TNF - α） and interleukin - 1 （IL - 1） were measured by immunohistochemistry. Results： In groups with atomization, the levels of arterial partial pressure of oxygen （PaO2） were higher, whereas the levels of partial pressure of carbon dioxide （PaCO2） in artery blood were lower than those of control and stomach infusion groups at the end of experiment （all P〈0.01）. There were no differences in the levels of PaO2 and PaCO2 between group D and E （both P〉0.05）. The pathological changes of lung tissues were severer in control group and stomach infusion groups than those in atomization groups. Pathologically, there was no significant difference between the two atomization groups. The positive high expressions of NF -κB, TNF -α and IL - 1 were lower, while the positive low expressions were higher in atomization groups than those in stomach infusion groups and control group （all P〈0. 05）. There were no differences in the above expressions between the two atomization groups and between stomach infusion groups and control group （all P〉0. 05）. Conclusion： Tea polyphenol has protective effect on lung in rabbits with ARDS when given through atomization. It can decrease the positive expressions of NF - κB, TNF -α and IL- 1 in the lung tissue, alleviate pathological changes, and improve clinical manifestation of ARDS. Tea polyphenol stomach infusion has no above effects.